Search Results (1,361)

Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD⁺ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article

Tomicus pilifer is a major pest that threatens Pinus koraiensis forests in the northeast region of China. In this study, we employed scanning electron microscopy (SEM) to observe the sensilla on the antennae, mouthparts, and legs of both male and female T. pilifer adults, analyzing the differences in sensillum types, external morphology, and quantities between sexes. The results revealed six types of sensilla on the antennae of both males and females, including sensilla trichoidea, sensilla zigzag, sensilla coeloconica, sensilla chaetica, Böhm bristles, and sensilla basiconica. Among these, sensilla basiconica was the most abundant, with four subtypes identified, and sensilla basiconica III was observed only on the male antennae, indicating sexual dimorphism in sensillum types. The mouthparts exhibited the greatest diversity in sensilla, with seven types identified: sensilla basiconica, sensilla twig basiconica, sensilla coeloconica, sensilla trichoidea, sensilla chaetica, sensilla zigzag, and sensilla digitiformia. Of these, sensilla basiconica and sensilla twig basiconica, responsible for olfactory or gustatory functions, were concentrated at the distal ends of the maxillary palps and labial palps. On the legs, sensilla trichoidea, sensilla zigzag, and sensilla chaetica were distributed on all segments. The findings of this study provide a scientific basis for further research into the olfactory and feeding behaviors, as well as electrophysiological studies, of T. pilifer. Full article

Several transient receptor potential vanilloid (TRPV) ion channels are proton-sensitive, and recent structural studies have identified poorly conserved mechanisms for the proton sensitivity of TRPV1, TRPV2 and TRPV5. While such detailed studies are lacking for TRPV3, three distinct intracellular motifs were suggested to be required for a direct channel activation by cytosolic acidification. In this study, we investigated if these mechanisms are also relevant for the activation of TRPV3 by weak acids. Wildtype (WT) and several mutants of human TRPV3 transiently expressed in HEK 293T cells were investigated by whole-cell patch clamp electrophysiology. Cells expressing TRPV3-WT generated membrane currents induced by acetic acid (HOAc), formic acid and carbonic acid at pH 5.0. Activation induced by HOAc was concentration-dependent and increased with decreasing pH values. HOAc also strongly potentiated TRPV3-mediated responses to carvacrol and heat. Among the three suggested motifs for the binding of intracellular protons, only the mutant TRPV3-Asp512Ala exhibited an almost complete loss of HOAc sensitivity. The mutation of two C-terminal charged residues (Gln689/Asp727) even resulted in a clear gain of function for both HOAc and heat, and the mutation of the 2-APB-binding site His426 did not significantly abrogate HOAc sensitivity. Finally, insertion of the recently identified binding site in TRPV2 for the weak acid probenecid into TRPV3 (Glu216His) resulted in an increased HOAc sensitivity. To conclude, our data confirm that TRPV3 is sensitized and activated by several weak acids. While Asp512 appears to be a critical intracellular proton-modulating site, a more profound understanding of the mechanisms dictating the proton sensitivity of TRPV3 may require structural studies. Full article

Orange spiny whitefly (Aleurocanthus spiniferus Quaintance) is a major pest with economic significance to tea plants, as both nymphs and adults suck plant sap and contribute to the development of tea sooty mold. The occurrence of this pest varies considerably among different tea cultivars, even within the same plantation. This study aims to characterize the bioactive constituents of tea volatiles mediating A. spiniferus host selection, and leverage these semiochemicals to develop effective field trapping systems. Through field investigations and Y-tube olfactometer tests, we identified two highly preferred tea cultivars (‘Huangjinya’ and ‘Fuding white tea’) and two cultivars (‘Baiye No. 1’ and ‘Longjing 43’) that were not preferred. Behavioral assays and gas chromatography-mass spectrometry (GC-MS) analysis revealed four attractive compounds [hexanol, (E)-2-hexenal, linalool, and (E,E)-α-farnesene] and two repellent compounds [nonanal and (Z)-3-hexenol] in the volatile emissions of the four cultivars. A hexane solution (10 µL) of nonanol, (Z)-3-hexenol, linalool, and (E,E)-α-farnesene at a concentration of 100 µg/µL was able to elicit an obvious electrophysiological (EAG) response. In field trials, the synergistic bait trap equipped with two types of attractants, 500 µL of hexane solution of the mixture of linalool and (E,E)-α-farnesene (3:1, v/v), and the mixture of linalool and (Z)-3-hexenol (3:1, v/v) at the concentration of 100 μg/μL, showed significantly higher attractant efficacy and selectivity. Overall, this study indicates that tea volatiles play a crucial role in the host selection of A. spiniferus, and the synthetic mixtures of tea volatiles have the potential to be developed as commercial plant-based attractants for adult A. spiniferus. This study contributes to the development of sustainable, environmentally friendly management strategies for a pest that is challenging to prevent and control. Full article

Voltage-gated Na⁺ channels (Nav) are the molecular determinants of action potential initiation and propagation. Among the nine voltage-gated Na⁺ channel isoforms (Nav1.1–Nav1.9), Nav1.2 and Nav1.6 are of particular interest because of their developmental expression profile throughout the central nervous system (CNS) and their association with channelopathies. Although the α-subunit coded by each of the nine isoforms can sufficiently confer transient Na⁺ currents (I_Na), in vivo these channels are modulated by auxiliary proteins like intracellular fibroblast growth factor (iFGFs) through protein–protein interaction (PPI), and probes developed from iFGF/Nav PPI complexes have been shown to precisely modulate Nav channels. Previous studies identified ZL0177, a peptidomimetic derived from a short peptide sequence at the FGF14/Nav1.6 PPI interface, as a functional modulator of Nav1.6-mediated I_Na⁺. However, the isoform specificity, binding sites, and putative physiological impact of ZL0177 on neuronal excitability remain unexplored. Here, we used automated planar patch-clamp electrophysiology to assess ZL0177’s functional activity in cells stably expressing Nav1.2 or Nav1.6. While ZL0177 was found to suppress I_Na in both Nav1.2- and Nav1.6-expressing cells, ZL0177 elicited functionally divergent effects on channel kinetics that were isoform-specific and supported by differential docking of the compound to AlphaFold structures of the two channel isoforms. Computational modeling predicts that ZL0177 modulates Nav1.2 and Nav1.6 in an isoform-specific manner, eliciting phenotypically divergent effects on action potential discharge. Taken together, these results highlight the potential of PPI derivatives for isoform-specific regulation of Nav channels and the development of therapeutics for channelopathies. Full article

Cirrhotic cardiomyopathy (CCM) is a cardiac dysfunction in patients with cirrhosis, occurring in the absence of structural heart disease. It increases perioperative risk, especially in liver transplantation, and may contribute to hepatorenal syndrome. Despite its clinical significance, CCM remains poorly understood and lacks effective treatments. This review aims to summarize recent findings on the pathogenesis of CCM and highlight potential therapeutic targets. A focused literature review was conducted using PubMed, Scopus, and Clarivate databases, selecting studies from the last five years. Included studies investigated molecular, cellular, and receptor-mediated mechanisms involved in CCM. Results: CCM results from neurohumoral, inflammatory, and electrophysiological disturbances. Key mechanisms involve dysfunction of β-adrenergic and muscarinic receptors, altered ion channels (potassium, L-type calcium), impaired sodium–calcium exchange, and suppression of the P2X7 receptor (P2X7R). Dysregulation of the CD73 (5’-nucleotidase, ecto-5’-nucleotidase)–A2 adenosine axis, along with effects from endocannabinoids, nitric oxide (NO) inhibition by tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), carbon monoxide (CO), and elevated galectin-3 (Gal-3), further contribute to myocardial dysfunction. Conclusions: CCM is a multifactorial condition linked to systemic and myocardial effects of cirrhosis. A deeper understanding of its mechanisms is essential for developing targeted therapies. Further research is needed to improve patient outcomes. Full article

Background: Obesity is a complex disorder with both metabolic and neurocognitive consequences, including impairments in prefrontal cortex (PFC)-dependent learning and memory. Combination pharmacotherapy may offer a more effective approach for addressing obesity-induced cognitive deficits. Objective: This study evaluated the effects of 30-day co-administration of lorcaserin (5-HT₂C agonist) and betahistine (H₁ agonist/H₃ antagonist) in reversing cognitive deficits in a diet-induced obesity (DIO) rat model. Methods: Male Lewis rats were subjected to DIO and administered lorcaserin (2 mg/kg) and betahistine (5 mg/kg), either alone or in combination, via intraperitoneally implanted osmotic minipumps for 30 days. Y-maze, novel object recognition, and object-in-place (OIP) tests were used to assess cognitive functions. In vivo electrophysiological recordings were employed to examine effects of the combination treatment on ventral tegmental area (VTA) dopaminergic neuron activity. Results: Obese Western-diet-fed rats showed lower discrimination scores in the OIP task, a behavioral test that engages PFC functions, while their performance in the Y-maze and novel object recognition tasks was similar to that of non-obese Control-diet-fed rats. Combination treatment with lorcaserin and betahistine significantly improved the OIP scores of obese rats. However, the combination treatment did not reduce body weight or obesity-associated morphometrical parameters. Electrophysiological recordings revealed a reduction in the number of spontaneously active dopaminergic neurons in the VTA of obese rats. Lorcaserin and betahistine co-treatment significantly increased the number of spontaneously active dopaminergic neurons of obese animals. Conclusions: These results demonstrate the potential of combination lorcaserin–betahistine treatment to reverse obesity-related cognitive deficits, possibly through enhancement of mesocortical dopaminergic neuron activity. Full article

Based on the photoconductive effect of photosensitive films, a designed light pattern was projected onto a hydrogenated amorphous silicon (a-Si:H) photosensitive chip to generate virtual light-induced electrodes for cellular electrical detection. To obtain high-quality cellular signals, this study aims to explore the effect of electrical excitation on a-Si:H photosensitive chip. Firstly, the electrochemical impedance spectroscopy (EIS) and volt-ampere characteristics of the a-Si:H photosensitive chip were characterized. EIS data were fitted to extract equivalent circuit models (ECMs) for both the chip and system. Then analog experiments were performed to verify the ECMs, and the results were consistent with the circuit simulation. Finally, applied alternating current (AC) or direct current (DC) signals to the chip and recorded the electrical signals of the cultured cardiomyocytes on the a-Si:H photosensitive chip. The results demonstrated that applying a high-frequency small AC signal to the chip reduced the background noise of the system by approximately 85.1%, and applying a DC bias increased the amplitude of the detection signal by approximately 142.7%. Consequently, the detection performance of the a-Si:H photosensitive chip for weak bioelectrical signals was significantly enhanced, advancing its applicability in cellular electrophysiological studies. Full article

Objectives: Chronic psychological stress among college students increases sensitivity to negative emotional stimuli. Emotion regulation, a critical coping mechanism, draws upon cognitive resources and may impair subsequent cognitive control. Physical exercise has been proposed as an effective intervention to enhance both emotional and cognitive functioning. This study investigated whether a 12-week structured exercise intervention could modulate emotion regulation outcomes and improve cognitive control in college students experiencing high psychological stress. Methods: Forty-seven college students, identified as highly stressed via the Chinese College Students Psychological Stress Scale, were randomly assigned to either an exercise group (n = 25) or a control group (n = 22). The exercise group participated in supervised rope-jumping sessions three times per week for 40 min, following ACSM guidelines, over 12 weeks. Before and after the intervention, participants completed tasks measuring two emotion regulation strategies—expressive suppression and cognitive reappraisal—and tasks assessing cognitive control. Results: A significant group × time × strategy interaction emerged for subjective emotional valence: following the intervention, the exercise group reported attenuated negative valence under expressive suppression. For subjective arousal, post-intervention ratings decreased under suppression but increased under reappraisal in the exercise group, suggesting strategy-specific modulation by physical activity. Regarding cognitive control, electrophysiological measures revealed that the P3 component showed a significant interaction: the exercise group exhibited enhanced P3 amplitudes in congruent versus incongruent conditions after the intervention. Moreover, P3 interference scores were significantly reduced post-intervention in the exercise group compared to both its pre-intervention baseline and the control group. Conclusions: A 12-week aerobic exercise intervention enhanced emotion regulation outcomes and improved cognitive control under high psychological stress. These findings underscore the utility of physical exercise as a non-pharmacological approach to bolster cognitive–affective resilience in young adults. Full article

The assessment of upper limb (UL) movement patterns plays a critical role in the rehabilitation of individuals with motor impairments resulting from neuromotor disorders, which significantly affect essential activities of daily living (ADLs) such as drinking and eating. However, conventional clinical evaluation methods often lack objective and quantitative insights into the biomechanics of movement. To enable accurate identification of pathological patterns, it is first necessary to establish normative biomechanical and electrophysiological benchmarks in healthy individuals. In this study, a previously developed, low-cost, wearable, and portable prototype device was employed to objectively assess UL movement. The system, specifically designed for clinical applicability, integrates surface electromyography (EMG) sensors and an inertial measurement unit (IMU) to capture muscle activity and kinematic data, respectively. Thirty healthy participants were recruited to perform standardized drinking and eating tasks. The analysis focused on characterizing muscle activation patterns and joint range of motion during different task phases. Results revealed consistent variations in muscle contraction and joint kinematics, allowing the identification of distinct activation profiles for key shoulder muscles. The findings contribute to the establishment of a normative dataset that can serve as a reference for the assessment of clinical populations. Such data are essential for informing rehabilitation strategies and developing predictive models of UL function during ADLs in individuals with neuromotor disorders. Full article

Renocardiac syndrome type 4 (RCS4) is a common comorbid pathology, but the mechanisms of kidney dysfunction-induced cardiac remodeling and the involvement of cardiac progenitor cells (CPCs) in this process remain unclear. The aim of this study was to investigate the structural and functional changes in the cardiac muscle in RCS4 induced by unilateral ureteral obstruction (UUO) and the role of nestin⁺ CPCs in these. Heart function and localization of nestin⁺ cells in the myocardium were assessed using nestin-GFP transgenic mice subjected to UUO for 14 and 28 days. UUO resulted in cardiac hypertrophy, accompanied by an elongation of the QRS wave on the ECG, decreased expression of Cxcl1, Cxcl9, and Il1b, reduced the number of CD11b⁺ cells, and increased in titin isoform parameters, such as T1/MHC and TT/MHC ratios, without changes in fibrosis markers. The number of nestin⁺ cells increased in the myocardium with increased duration of UUO and displayed an SCA-1⁺TBX5⁺ phenotype, consistent with CPCs. Thus, cardiac pathology in RCS4 was manifested by cardiomyocyte hypertrophy with changes in the electrophysiological phenotype of the heart, not accompanied by fibrosis or inflammation. Nestin⁺ cardiac cells retained the CPC phenotype during UUO, and their number increased, which suggests their participation in regenerative processes in the heart. Full article

Introduction: Learning disabilities (LD) compromise academic achievement in approximately 5–10% of school-aged children, yet the neurophysiological signatures that could facilitate earlier detection or stratification remain poorly defined. Resting-state electroencephalography (rs-EEG) offers millisecond resolution and is cost-effective, but its findings have never been synthesized systematically across pediatric LD cohorts. Methods: Following a PROSPERO-registered protocol (CRD420251087821) and adhering to PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, Scopus, and PsycINFO through 31 March 2025 for peer-reviewed studies that recorded eyes-open or eyes-closed rs-EEG using ≥ 4 scalp electrodes in children (≤18 years) formally diagnosed with LD, and compared the results with typically developing peers or normative databases. Four reviewers independently screened titles and abstracts, extracted data, and assessed the risk of bias using ROBINS-I. Results: Seventeen studies (704 children with LD; 620 controls) met the inclusion criteria. The overall risk of bias was moderate, primarily due to small clinic-based samples and inconsistent control for confounding variables. Three consistent electrophysiological patterns emerged: (i) a 20–60% increase in delta/theta power over mesial-frontal, fronto-central and left peri-Sylvian cortices, resulting in markedly elevated θ/α and θ/β ratios; (ii) blunting or anterior displacement of the posterior alpha rhythm, particularly in language-critical temporo-parietal regions; and (iii) developmentally immature connectivity, characterized by widespread slow-band hypercoherence alongside hypo-connected upper-alpha networks linking left-hemisphere language hubs to posterior sensory areas. These abnormalities were correlated with reading, writing, and IQ scores and, in two longitudinal cohorts, they partially normalized in parallel with academic improvement. Furthermore, a link between reduced posterior/overall alpha and neuroinflammation has been found. Conclusions: Rs-EEG reveals a robust yet heterogeneous electrophysiological profile of pediatric LD, supporting a hybrid model that combines maturational delay with persistent circuit-level atypicalities in some children. While current evidence suggests that rs-EEG features show promise as potential biomarkers for LD detection and subtyping, these findings remain preliminary. Definitive clinical translation will require multi-site, dense-array longitudinal studies employing harmonized pipelines, integration with MRI and genetics, and the inclusion of EEG metrics in intervention trials. Full article

Background and Objectives: Limb–girdle muscular dystrophies (LGMDs) are a group of muscular dystrophies characterized by predominantly proximal-muscle weakness, with a highly heterogeneous genetic etiology. Despite recent efforts, the epidemiology of LGMDs is still under-evaluated. However, a better understanding of the distribution and genetic characteristics of LGMDs is required to optimize the diagnostic process and to address future research. Therefore, the aim of the present study is to investigate and identify new pathogenic variants, to better characterize LGMDs in Sicily. Methods: We enrolled patients with genetic and clinical diagnosis of LGMD referred to our clinic between the years 2019 and 2025. A targeted next-generation-sequencing (NGS) panel was performed, based on the reported disease frequency. A retrospective analysis of the clinical, laboratory, electrophysiological, and histological features was performed. Results: A total of 28 LGMDs patients aged 56.6 years (47.2–60.5 IQR) were identified (16 males, 57%). A molecular diagnosis was achieved in 24 (85.7%) of patients, most commonly carrying mutations in CAPN3 (14 patients, 50%), followed by DYSF, LAMA2, ANO5, FKTN and TTN genes. Pathogenic variants in CAPN3 and LAMA2 were associated with earlier onset and longer disease duration, whereas ANO5 presented later with a milder course. Cardiac involvement was observed more frequently in patients with LAMA2 and FKTN mutations. Association between heterozygous mutations in the CAPN3 and DYSF, as well as between CAPN3 and DMD variants were reported. Discussion: The findings of this study provide valuable insights into the epidemiology of LGMDs in the Western Sicily, offering important contributions to genotype–phenotype correlations. Our analysis highlights the role of genetic diagnosis in achieving accurate classification of the disease and optimizing clinical management. Full article

Background/Objectives: Endozepines known as the endogenous ligands of benzodiazepine-binding sites, include the diazepam binding inhibitor (DBI) and its processing products, the triakontatetraneuropeptide (TTN) and the octadecaneuropeptide (ODN). Despite indisputable evidence of the binding of ODN on GABA_AR-BZ-binding sites, their action on this receptor lacks compelling electrophysiological observations, with some studies reporting that ODN acts as a negative allosteric modulator (NAM) of GABA_AR while others suggest the opposite (positive allosteric modulation, PAM effect). All these studies were carried out in vitro with various neuronal cell types. To further elucidate the role of ODN in neuronal excitability, we tested its effect in vivo in the cerebral cortex of the anesthetized mouse. Methods: Spontaneous neuronal spikes were recorded by means of an extracellular pipette, in the vicinity of which ODN was micro-infused, either at a high dose (10⁻⁵ M) or low dose (10⁻¹¹ M). Results: ODN at a high dose induced a significant increase in neuronal spiking. This effect could be antagonized by the GABA_AR-BZ-binding site blocker flumazenil. In sharp contrast, at low concentrations, ODN reduced neuronal spiking with a magnitude similar to GABA itself. Interestingly, this decrease in neuronal activity by low dose of ODN was not flumazenil-dependent, suggesting that this effect is mediated by another receptor. Finally, we show that astrocytes in culture, known to be stimulated by picomolar doses of ODN via a GPCR, increased their export of GABA when stimulated by low dose of ODN. Conclusion: Our results confirm the versatility of ODN in the control of GABA transmission, but suggest that its PAM-like effect is, at least in part, mediated via an astrocytic non-GABA_AR ODN receptor release of GABA. Full article

Background: Obesity is clinically known to be associated with an increased risk and aggravated pathology of Alzheimer’s disease (AD). A high-fat diet (HFD), the major contributor to obesity, induces neuroinflammation and central insulin resistance, both of which are linked to synaptic dysfunction. Our previous studies demonstrated that avenanthramide-C (Avn-C), a natural oat-derived phenolic compound, exerts anti-inflammatory effects and alleviates synaptic dysfunction in conventional AD models. The present study aimed to elucidate the underlying mechanisms of Avn-C in obesity-accelerated AD. Methods: Two-month-old male 5×FAD mice were fed an HFD to induce obesity and then treated with Avn-C. Cognitive performance, synaptic function, and structure were assessed via behavioral tests, electrophysiological recordings, and Golgi–Cox staining, respectively. Cytokine levels were quantified using ELISA and Western blotting. To explore the underlying mechanism, the NOD1 agonist C12-iE-DAP was administered to evaluate its effect on Avn-C-mediated neuroprotection. Results: Avn-C reduced Aβ deposition, enhanced the expression of synapse proteins, and restored synaptic plasticity, thereby improving both spatial and recognition memory in obese 5×FAD mice. Furthermore, Avn-C reduced neuroinflammation by inhibiting the NOD1/RIP2/NF-κB signaling pathway. Co-treatment with C12-iE-DAP abolished the beneficial effects of Avn-C on neuroinflammation, Aβ pathology, and cognitive function. Conclusions: These results suggest that Avn-C mitigates obesity-exacerbated AD-like pathological features by suppressing NOD1/RIP2/NF-κB-mediated neuroinflammation and could be a new potential therapeutic strategy for obesity-associated AD. Full article